Innate Immune Memory and the Host Response to Infection

Abstract

Unlike the adaptive immune system, the innate immune system has classically been characterized as being devoid of memory functions. However, recent research shows that innate myeloid and lymphoid cells have the ability to retain memory of prior pathogen exposure and become primed to elicit a robust, broad-spectrum response to subsequent infection. This phenomenon has been termed innate immune memory or trained immunity. Innate immune memory is induced via activation of pattern recognition receptors and the actions of cytokines on hematopoietic progenitors and stem cells in bone marrow and innate leukocytes in the periphery. The trained phenotype is induced and sustained via epigenetic modifications that reprogram transcriptional patterns and metabolism. These modifications augment antimicrobial functions, such as leukocyte expansion, chemotaxis, phagocytosis, and microbial killing, to facilitate an augmented host response to infection. Alternatively, innate immune memory may contribute to the pathogenesis of chronic diseases, such as atherosclerosis and Alzheimer's disease.

Figure 1:

The biological basis of innate immune memory. Treatment with PAMPS such as β-glucan, MPLA or CpG ODN induces epigenetic, metabolic and functional reprogramming of the innate immune system resulting in augmented resistance to local and systemic infection.

Figure 2:

Functional, metabolic and epigenetic alterations driving innate immune memory. Training of innate leukocytes and non-leukocyte populations induces functional alterations that facilitate innate leukocyte progenitor expansion, leukocyte recruitment, phagocytosis and microbial killing. These alterations are enabled, in part, by epigenetic remodeling and metabolic reprogramming.